US7074784B2ExpiredUtilityPatentIndex 89
Medicaments against viral diseases
Est. expiryMar 16, 2020(expired)· nominal 20-yr term from priority
Inventors:GOLDMANN SIEGFRIEDSTOLTEFUSS JURGENNIEWOHNER LEGAL REPRESENTATIVESCHLEMMER KARL-HEINZKELDENICH JORGPAESSENS ARNOLDGRAEF ERWINWEBER OLAFDERES KARL
A61P 31/12C07D 401/04A61P 1/16C07D 401/14C07D 417/04
89
PatentIndex Score
33
Cited by
8
References
14
Claims
Abstract
Novel dihydropyrimidines and combinations thereof with other antiviral agents, suitable for combating HBV infections.
Claims
exact text as granted — not AI-modifiedThe invention claimed is:
1. A compound of the formula
and the isomeric form thereof
in which
R 1 , R 2 are, independently of one another, hydrogen, fluorine, chlorine or bromine,
R 3 is C 1 –C 4 -alkyl,
X is a methylene or ethylene group,
Z is NR 4 R 5 or pyridyl,
R 4 is C 1 –C 4 -alkyl which may be substituted by hydroxyl or C 1 –C 4 -alkoxycarbonyl, or is benzyl,
R 5 is C 1 –C 4 -alkyl which may be substituted by hydroxyl, or
R 4 and R 5 together with the nitrogen atom to which they are bonded are an imidazolyl, triazolyl or tetrazolyl ring or a radical of the formula
in which
a is zero or 1 and
Y is CH 2 , CH 2 CH 2 , —O— or —S—, and
R 6 is pyridyl which is substituted once to twice by fluorine, or is thiazolyl, and the salts thereof.
2. A compound as claimed in claim 1 , in which
R 4 and R 5 together with the nitrogen atom to which they are bonded form a morpholinyl or thiomorpholinyl ring,
and the salts thereof.
3. A compound as claimed in claim 1 , in which
R 1 , R 2 are, independently of one another, fluorine, chlorine or bromine,
and the salts thereof.
4. A compound as claimed in claim 1 , in which
R 1 , R 2 are, independently of one another, fluorine, chlorine or bromine, and
R 4 and R 5 together with the nitrogen atom to which they are bonded form a morpholinyl or thiomorpholinyl ring,
and the salts thereof.
5. A compound selected from the group consisting of:
6. A process for preparing the compounds as claimed in claim 1 , by
[A] reacting compounds of the formula
in which
R 1 to R 3 , X and Z have the meanings indicated in claim 1 ,
with amidines of the formula
in which
R 6 has the meaning indicated in claim 1 ,
or the salts thereof, or
[B] reacting compounds of the formula
in which
R 3 , X and Z have the meanings indicated in claim 1 , in a one-stage process with aldehydes of the formula
in which
R 1 and R 2 have the meanings indicated in claim 1 , and amidines of the formula
in which R 6 has the meanings indicated in claim 1 , or the salts thereof, or else
[C] where X in formula (I) is a methylene group, reacting compounds of the formula
in which
R 1 to R 3 and R 6 have the meanings indicated in claim 1 , and
Y is a nucleophilically replaceable group,
with compounds of the formula
in which
R 4 and R 5 have the meanings indicated claim 1 , or else
[D] where X in formula (I) is an ethylene group, reacting compounds of the formula
in which
R 1 to R 5 have the meanings indicated in claim 1 , with amidines of the formula
in which
R 6 has the meanings indicated in claim 1 ,
or the salts thereof.
7. A process for preparing the compounds as claimed in claim 1 , by
[A] firstly converting aldehydes of the formula
in which
R 1 and R 2 have the meanings indicated in claim 1 , with β-keto esters of the formula
in which
R 3 , X and Z have the meanings indicated in claim 1 , into benzylidene compounds of the formula
and then reacting the latter with amidines of the formula
in which
R 6 has the meaning indicated in claim 1 ,
or the salts thereof, or
[B] reacting compounds of the formula (III) in a one-stage process with aldehydes (II) and amidines (V) or the salts thereof, or else
[C] where X in formula (I) is a methylene group, reacting compounds of the formula
in which
R 1 to R 3 and R 6 have the meanings indicated in claim 1 , and
Y is a nucleophilically replaceable group,
with compounds of the formula
in which
R 4 and R 4 have the meanings indicated in claim 1 , or else
[D] where X in formula (I) is an ethylene group, converting compounds of the formula
in which
R 1 to R 3 have the meanings indicated in claim 1 , with immonium salts of the formula
in which
R 4 and R 5 have the meanings indicated in claim 1 , into compounds of the formula
and then reacting the latter with amidines of the formula (V) or the salts thereof.
8. A compound of the formula
in which
R 1 , R 2 , R 3 and R 6 have the meanings indicated in claim 1 .
9. A method of treating hepatitis B infection, comprising administering to a mammal an effective amount of a compound of claim 1 .
10. A method of treating diseases caused by infection with hepatitis B virus, comprising administering to a mammal an effective amount of a compound of claim 1 .
11. The method of claim 10 wherein said disease is hepatitis.
12. The method of claim 10 wherein said disease is cirrhosis of the liver.
13. The method of claim 10 wherein said disease is hepatocellular carcinoma.
14. A pharmaceutical preparation comprising one or more compounds of claim 1 in combination with a pharmaceutically acceptable carrier.Cited by (0)
No later patents cite this yet.
References (0)
No backward citations on record.